Donepezil or its salt, whose chemical name is 2-[(1-benzyl-4-piperidinyl)methyl]-5,6-dimethoxyindan-1-one, is an acetylcholinesterase inhibitor used as a therapeutic agent for treating dementia.
Dementia occurs primarily in the elderly. Elderly people often have difficulty in swallowing and a lot of patients suffering from fairly advanced dementia also have difficulty in taking an oral formulation. In addition, in case of oral administration, plasma drug concentrations may increase and decrease very rapidly, which results in causing side effects. Therefore, there is a need for formulations capable of maintaining a plasma concentration uniformly and continuously. For example, EP1437130A1 has disclosed a transdermal delivery system containing an antidementia agent such as donepezil. The transdermal delivery system has a structure in which the antidementia agent such as donepezil is dispersed in an adhesive; and is designed so as to maintain the plasma drug concentration uniformly for more than 12 hours when applied to the skin. And also, WO2007/129427 has disclosed a transdermal delivery system having a triple-layer structure including an adhesive layer, a drug-containing layer, and an intermediate layer.
Meanwhile, for normal patients suffering from dementia, it is necessary to design a transdermal delivery system capable of maintaining the blood concentration of a drug for 1 day to several days, e.g., for more than 1 day, preferably for more than about 1 week. Such a transdermal delivery system requires using relatively high amounts of a drug, e.g., donepezil. However, if the amount of donepezil is increased in conventional transdermal delivery systems, donepezil become crystallized in the formulations, thereby causing problems such as reduction in the adhesive strength. Furthermore, in case of the transdermal delivery system of a triple-layer form designed to control the release rate of donepezil, the production process thereof become complicated and difficult; and there are disadvantages such as poor economic efficiency.
In addition, even when a transdermal delivery system acting for a long time is designed through completely dissolving donepezil with a conventional solubilizing agent such as surfactants, rapid release dumping phenomenon occurs during the use thereof. Therefore, it is required to design a transdermal delivery system capable of inhibiting the release dumping problems effectively.